Development of spirulina for the manufacture and oral delivery of protein therapeutics

The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, in...

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Published inNature biotechnology Vol. 40; no. 6; pp. 956 - 964
Main Authors Jester, Benjamin W., Zhao, Hui, Gewe, Mesfin, Adame, Thomas, Perruzza, Lisa, Bolick, David T., Agosti, Jan, Khuong, Nhi, Kuestner, Rolf, Gamble, Caitlin, Cruickshank, Kendra, Ferrara, Jeremy, Lim, Rachelle, Paddock, Troy, Brady, Colin, Ertel, Stacey, Zhang, Miaohua, Pollock, Alex, Lee, Jamie, Xiong, Jian, Tasch, Michael, Saveria, Tracy, Doughty, David, Marshall, Jacob, Carrieri, Damian, Goetsch, Lauren, Dang, Jason, Sanjaya, Nathaniel, Fletcher, David, Martinez, Anissa, Kadis, Bryce, Sigmar, Kristjan, Afreen, Esha, Nguyen, Tammy, Randolph, Amanda, Taber, Alexandria, Krzeszowski, Ashley, Robinett, Brittney, Volkin, David B., Grassi, Fabio, Guerrant, Richard, Takeuchi, Ryo, Finrow, Brian, Behnke, Craig, Roberts, James
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.06.2022
Nature Publishing Group
Springer Nature
Subjects
631/1647/1511
631/61/185
631/61/2297
631/61/51/2314
Agriculture
Antibodies
BASIC BIOLOGICAL SCIENCES
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Biotechnology & Applied Microbiology
Campylobacter
Chromosomes
Cyanobacteria
Food safety
Genetic engineering
Infant mortality
Life Sciences
Microorganisms
Photosynthesis
Proteins
Refrigeration
Safety
Spirulina
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Abstract The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms. Spirulina is used to manufacture a therapeutic antibody against campylobacter.
AbstractList The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms. Spirulina is used to manufacture a therapeutic antibody against campylobacter.
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter-a major cause of infant mortality in the developing world-prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter-a major cause of infant mortality in the developing world-prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter-a major cause of infant mortality in the developing world-prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic tools. Here we report genetic engineering methods for stable, high-level expression of bioactive proteins in spirulina, including large-scale, indoor cultivation and downstream processing methods. Following targeted integration of exogenous genes into the spirulina chromosome (chr), encoded protein biopharmaceuticals can represent as much as 15% of total biomass, require no purification before oral delivery and are stable without refrigeration and protected during gastric transit when encapsulated within dry spirulina. Oral delivery of a spirulina-expressed antibody targeting campylobacter—a major cause of infant mortality in the developing world—prevents disease in mice, and a phase 1 clinical trial demonstrated safety for human administration. Spirulina provides an advantageous system for the manufacture of orally delivered therapeutic proteins by combining the safety of a food-based production host with the accessible genetic manipulation and high productivity of microbial platforms.Spirulina is used to manufacture a therapeutic antibody against campylobacter.
Author Grassi, Fabio
Robinett, Brittney
Finrow, Brian
Zhao, Hui
Martinez, Anissa
Volkin, David B.
Bolick, David T.
Goetsch, Lauren
Sigmar, Kristjan
Nguyen, Tammy
Dang, Jason
Kuestner, Rolf
Takeuchi, Ryo
Randolph, Amanda
Saveria, Tracy
Doughty, David
Krzeszowski, Ashley
Gamble, Caitlin
Roberts, James
Khuong, Nhi
Paddock, Troy
Behnke, Craig
Lee, Jamie
Taber, Alexandria
Jester, Benjamin W.
Agosti, Jan
Pollock, Alex
Perruzza, Lisa
Ertel, Stacey
Marshall, Jacob
Xiong, Jian
Tasch, Michael
Cruickshank, Kendra
Carrieri, Damian
Afreen, Esha
Gewe, Mesfin
Brady, Colin
Adame, Thomas
Ferrara, Jeremy
Guerrant, Richard
Sanjaya, Nathaniel
Lim, Rachelle
Zhang, Miaohua
Kadis, Bryce
Fletcher, David
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35314813$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright The Author(s) 2022. corrected publication 2022
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CorporateAuthor Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
CorporateAuthor_xml – name: Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
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Snippet The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic...
The use of the edible photosynthetic cyanobacterium Arthrospira platensis (spirulina) as a biomanufacturing platform has been limited by a lack of genetic...
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631/61/185
631/61/2297
631/61/51/2314
Agriculture
Antibodies
BASIC BIOLOGICAL SCIENCES
Bioinformatics
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Biotechnology & Applied Microbiology
Campylobacter
Chromosomes
Cyanobacteria
Food safety
Genetic engineering
Infant mortality
Life Sciences
Microorganisms
Photosynthesis
Proteins
Refrigeration
Safety
Spirulina
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Title Development of spirulina for the manufacture and oral delivery of protein therapeutics
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